Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Rapid personalized AMR diagnostics using two-dimensional antibiotic resistance profiling strategy employing a thermometric NDM-1 biosensor

Meng, Qinglai ; Liu, Shichao ; Meng, Jinhua ; Feng, Jiao ; Mecklenburg, Michael ; Zhu, Lei ; Zhou, Lifang ; Bülow, Leif LU ; Liu, Jianyi and Song, Dewei , et al. (2021) In Biosensors and Bioelectronics 193.
Abstract

Antimicrobial resistance (AMR) threatens global public health and modern surgical medicine. Expression of β-lactamase genes is the major mechanism by which pathogens become antibiotic resistant. Pathogens expressing extended spectrum β-lactamases (ESBL) and carbapenemases (CP) are especially difficult to treat and are associated with increased hospitalization and mortality rates. Despite considerable effort, identification of ESBLs and CPs in a clinically relevant timeframe remains challenging. In this study, a two-dimensional AMR profiling assay strategy was developed employing panels of antibiotics (penicillins, cephamycins, oximino-cephalosporins and carbapenems) and β-lactamases inhibitors (avibactam and EDTA). The assay required... (More)

Antimicrobial resistance (AMR) threatens global public health and modern surgical medicine. Expression of β-lactamase genes is the major mechanism by which pathogens become antibiotic resistant. Pathogens expressing extended spectrum β-lactamases (ESBL) and carbapenemases (CP) are especially difficult to treat and are associated with increased hospitalization and mortality rates. Despite considerable effort, identification of ESBLs and CPs in a clinically relevant timeframe remains challenging. In this study, a two-dimensional AMR profiling assay strategy was developed employing panels of antibiotics (penicillins, cephamycins, oximino-cephalosporins and carbapenems) and β-lactamases inhibitors (avibactam and EDTA). The assay required the development of a novel biosensor that employed New Delhi metallo-β-lactamase-1 (NDM-1) as the sensing element. Functionally probing β-lactamase activity using substrates and inhibitors combinatorically increased the informational content that enabled the development of assays capable of simultaneous, differential identification of multiple β-lactamases expressed in a single bacterial isolate. More specifically, the assay enabled the simultaneous identification of ESBL and CP in mock samples, as well as in an engineered construct which co-expressed these β-lactamases. The NDM-1 biosensor assay was 16 times and 8 times more sensitive than the ESBL Nordmann/Dortet/Poirel (NDP) and Carba Nordmann/Poirel (NP) assays, respectively. In a retrospective study, NDM-1 biosensor assays were able to differentially identify ESBLs, metallo-CPs and serine-CPs β-lactamases in 23 clinical isolates with 100% accuracy. An assay algorithm was developed which accelerated data analytics reducing turnaround to <1 h. The assay strategy integrated with AI-based data analytics has the potential to provide physicians with a comprehensive readout of patient AMR status.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Antimicrobial resistance, Carbapenemase, ESBL, NDM-1, Precision diagnostics, Thermometric biosensor
in
Biosensors and Bioelectronics
volume
193
article number
113526
publisher
Elsevier
external identifiers
  • scopus:85111262334
  • pmid:34325239
ISSN
0956-5663
DOI
10.1016/j.bios.2021.113526
language
English
LU publication?
yes
id
71bda039-34f1-44c1-93fb-55a5d91cdafc
date added to LUP
2021-08-24 14:37:51
date last changed
2024-06-15 15:09:48
@article{71bda039-34f1-44c1-93fb-55a5d91cdafc,
  abstract     = {{<p>Antimicrobial resistance (AMR) threatens global public health and modern surgical medicine. Expression of β-lactamase genes is the major mechanism by which pathogens become antibiotic resistant. Pathogens expressing extended spectrum β-lactamases (ESBL) and carbapenemases (CP) are especially difficult to treat and are associated with increased hospitalization and mortality rates. Despite considerable effort, identification of ESBLs and CPs in a clinically relevant timeframe remains challenging. In this study, a two-dimensional AMR profiling assay strategy was developed employing panels of antibiotics (penicillins, cephamycins, oximino-cephalosporins and carbapenems) and β-lactamases inhibitors (avibactam and EDTA). The assay required the development of a novel biosensor that employed New Delhi metallo-β-lactamase-1 (NDM-1) as the sensing element. Functionally probing β-lactamase activity using substrates and inhibitors combinatorically increased the informational content that enabled the development of assays capable of simultaneous, differential identification of multiple β-lactamases expressed in a single bacterial isolate. More specifically, the assay enabled the simultaneous identification of ESBL and CP in mock samples, as well as in an engineered construct which co-expressed these β-lactamases. The NDM-1 biosensor assay was 16 times and 8 times more sensitive than the ESBL Nordmann/Dortet/Poirel (NDP) and Carba Nordmann/Poirel (NP) assays, respectively. In a retrospective study, NDM-1 biosensor assays were able to differentially identify ESBLs, metallo-CPs and serine-CPs β-lactamases in 23 clinical isolates with 100% accuracy. An assay algorithm was developed which accelerated data analytics reducing turnaround to &lt;1 h. The assay strategy integrated with AI-based data analytics has the potential to provide physicians with a comprehensive readout of patient AMR status.</p>}},
  author       = {{Meng, Qinglai and Liu, Shichao and Meng, Jinhua and Feng, Jiao and Mecklenburg, Michael and Zhu, Lei and Zhou, Lifang and Bülow, Leif and Liu, Jianyi and Song, Dewei and Wu, Changxin and Xie, Bin}},
  issn         = {{0956-5663}},
  keywords     = {{Antimicrobial resistance; Carbapenemase; ESBL; NDM-1; Precision diagnostics; Thermometric biosensor}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Biosensors and Bioelectronics}},
  title        = {{Rapid personalized AMR diagnostics using two-dimensional antibiotic resistance profiling strategy employing a thermometric NDM-1 biosensor}},
  url          = {{http://dx.doi.org/10.1016/j.bios.2021.113526}},
  doi          = {{10.1016/j.bios.2021.113526}},
  volume       = {{193}},
  year         = {{2021}},
}